Myosin V functions as an actin-dependent ATPase. In Drosophila it is enriched in the brain. Identification of a mutant bearing a P-lacW insertion 600 bp from the ATG initiation site in the myosin V gene of Drosophila melanogaster has enabled us to study the effects of limited myosin V on the developing fly. Maternally contributed mRNA may support the survival of the homozygote mutant larva into the later larval stages since there are no apparent behavioral or developmental defects in either embryos or in early instar larvae. Neurological problems are first evident in the 3rd instar, where the distal portion of the larva is paralyzed which decreases the force and propagation of the peristaltic wave which propels them forward. These neurological defects are magnified in the adult stages in which mutants are slow moving and unable to jump or fly. They also exhibit a general tremor of their head and legs. This chorea progresses rapidly, with newly hatched flies tending to move around at an almost normal rate, with movement becoming slower and less coordinated until death at 1 week. The homozygous P-element inserted flies are either severe hypomorphs or functional nulls for myosin V as no protein could be detected by Western blotting with a myosin V antibody from quantities of fly heads that yield an easily detectable signal in wild type and heterozyogotes. We plan to use these flies as the background for transgenic rescue experiments with myosin V constructs. In addition, we have cloned a novel myosin VII isoform from Drosophila and will be studying its properties.